Aminobutyric acid fungicides

ABSTRACT

Novel aminobutyric acids derivatives and methods for protecting crops against fungal diseases by applying to the crops or their locus a composition containing an effective amount of said derivatives.

CROSS REFERENCE TO RELATED APPLICATION

The present application is the national stage under 35 U.S.C. 371 ofPCT/IL97/00423, filed Dec. 24, 1997.

The present invention concerns a novel method to protect plants frompathogenic attack.

BACKGROUND OF THE INVENTION

The use of threo-DL-β-methylaspartic acid and of DL-β-aminobutyric acidfor the control of root rot of peas caused by Aphanomyces euteichesDrechs, has been described (Papavizas, Plant Disease Reporter, 48,537-541 (1964), Papavizas, Plant Disease Reporter, 51, 125-129 (1967).

The use of D-alaninie, D-and DL leucine and DL-α-aminobutyric acid at0.03 M was described to reduce scab in apple caused by Venturiainaequalis (Kuc et al., 49: 313-315, 1959).

Van Andel, showed (Tijdschur. Plantenziekten. 64: 307-327, 1958) thatDL-serine, D-serine (and to a lesser extent L-serine), phenylserine,DL-threonine but not DL-α aminobutyric acid nor DL-β aminobutyric acidbehaved as chemothrerpeutants against the fungus cladosporiumcucumerinum on cucumber (Ibid. page 318). Oort and Van Andel (1960,Mededel. Landsborowhager school Dpzoekingssta. Staat Gent 25: 981-992)showed that DL-β-aminobutyric acid applied to leaves of tomato protectedthose leaves against Phytophthora infestans (page 987).

Various derivatives of DL-β-aminobutyric acid and β-aminocrotonic acidhave been described in the patent literature as fungicides againstPhytophthora infestans in tomato and Plasmopara viticola in grapes(German Patent No. 1,120,802).

Co-pending Israel Patent Application No. 111,824 describes thepreparation and use of similar compounds which induce local and systemicresistance of crops against fungal diseases.

OBJECTIVES OF THE INVENTION

It is the objective of the present invention to provide compounds havingimproved activity against fungi as compared with the compounds of theco-pending Israel patent application 111,824.

SUMMARY OF THE INVENTION

We have found novel compounds of the formula (I):

wherein:

R₁ and R₂ are independently hydrogen, C₁₋₈ alkyl, phenyl, and phenylC₁₋₄ alkyl

R₃ is C₁₋₂₃ straight or branched or a cyclic alkyl or alkenyl;alkoxyalkyl; halogenated alkyl, phenyl, or benzyl; alkyl phenyl;

R₄ and R₅ are independently hydrogen or C₁₋₈ alkyl;

R₆ is hydrogen; C₁₋₈ alkyl; C₂₋₈ alkanoyl; phenyl C₁₋₄ alkyl, benzoylwherein the phenyl moiety is optionally substituted by one or morehalogen atoms or alkyl groups C₂₋₈ alkoxycarbonyl; CONHR₈ wherein R₈ ishydrogen, C₁₋₈ alkyl, phenyl, phenyl C₁₋₄; phenyl C₂₋₄ alkyloxycarbonyl;

R₇ is benzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl;

X is O or NH and salts thereof; and the crop is selected from tomatoes,potatoes, cereals, grapes, melon, wheat and cucumber.

We have also found a novel method of protecting a crop against fungaldiseases caused by fungi by applying to the crop or its locus acomposition containing an effective amount of a compound of the formula(I).

DETAILED DESCRIPTION OF THE INVENTION

Alkyl as used herein refers to straight chains, branched and cyclicforms and preferably contain one to ten carbon atoms.

R₁ and R₂ are preferably independently hydrogen, methyl or phenyl, morepreferably R₁ is hydrogen or methyl and R₂ is hydrogen.

R₃ is preferably C₁₋₁₂ straight or branched or a cyclic alkyl oralkenyl, phenyl, benzyl, or alkyl phenyl.

R₄ and R₅ are preferably independently hydrogen or C₁₋₄ alkyl, morepreferably R₄ is hydrogen or methyl and R₅ is hydrogen.

R₆ is preferably hydrogen, C₁₋₅ alkyl; and most preferred hydrogenmethyl.

R₇ is benzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl.

Preferred compounds of the invention are:

D,L N-benzenesulfonyl-3-aminobutyranilide;

D,L-N-β-methylbenzoyl-3-aminobutyric acid n-octyl ester;

N-β-methylbenzoyl-3-aminobutyric acid sec butyl ester;

D,L-N-3,4-dichloro benzoyl-3-aminobutyric acid n-octyl ester;

D,L-N-4-chlorobenzoyl-3-aminobutyric acid-2-chloro ethyl ester,

D,L-N-benzensulfonyl-3-amino N-benzyl butyramide;

D,L-N-benzoyl-3-aminobutyric acid 2-chloroethyl ester:

N-β-methylbenzoyl--3-amiobutyric acid 1-methyl-1-pentyl ester;

D,L-N-benzenesulfonyl-3-aminobutyric acid, n-octyl ester;

N-benzenesulfonyl-3-aminobutyric acid-sec-butyl ester;

N-benzenesulfonyl-3-aminobutyric acid-1-methyl-i -butyl ester;

D,L N-4-methoxybenzoyl-3-aminobutyric acid heptyl ester

D,L N-3,5-dimethylbezoyl-3-aminobutyric acid heptyl ester

D,L N-2,6-difluorobenzoyl-3-aminobutyric acid heptyl ester

D,L N-4-tertbutylbenzoyl-3-aminobutyric acid heptyl ester

D,L N-4-methylbenzenesulfonyl-3-aminobutyric acid i-methylpentyl ester

D,L N-benzenesulfonyl-3-aminobutyric acid 3-phenylpropyl ester

D,L N-4-cholrobenzoyl-3-aminobutyric acid 1-methylpentyl ester

D,L N-benzenesulfonyl-3-aminobutyric acid 2-(trichloromethyl)ethyl ester

D,L N-4-methylbenzenesulfonyl-3-aminobutyric 1-methylpropyll ester

D,L N-3,4-dimethylbezoyl-3-aminobutyric acid 1-methylbutyl ester

D,L N-3-methylbezoyl-3-aminobutyric acid heptyl ester

D,L N-3,5-dimethylbezoyl-3-aminobutyric acid 1-methylpentyl ester

D,L N-2,6-dichlorobenzoyl-3-aminobutyric acid heptyl ester

D,L N-2,6-dichlorobenzoyl-3-aminobutyric acid 2-methylpentyl ester

D,L N-4-methylbenzoyl-3-aminobutyric acid 3-phenylpropyl ester

D,L N-3,5-dimethylbezoyl-3-aminobutyric acid 2-chloroethyl ester

D,L N-4-methoxybenzoyl-3-aminobutyric acid 2-chloroethyl ester

D,L N-benzoyl-3-aminobutyric acid 2-(trichloromethyl)ethyl ester

D,L N-4-cholrobenzoyl-3-aminobutyric acid heptyl ester

D,L N-benzenesulfonyl-3-aminobutyric acid 1-methyl-2-methoxyethyl ester

D,L N-2-methylbezoyl-3-aminobutyric acid heptyl ester

D,L N-4-methylbenzenesulfonyl-3-aminobutyric acid 2-bromoethyl ester

D,L N-4-methylbenzenesulfonyl-3-aminobutyric acid heptyl ester

D,L N-4-chlorobenzenesulfonyl-3-aminobutyric acid propyl ester

D,L N-4-methylbenzoyl-3-aminobutyric acid 2-(trichloromethyl)ethyl ester

D,L N-4-methylbenzoyl-3-aminobutyric acid cyclohexyl ester

D,L N-benzoyl-3-aminobutyric acid cyclohexyl ester

D,L N-benzenesulfonyl-3-aminobutyric acid cyclohexyl ester

D,L N-4-chlorobenzenesulfonyl-3-aminobutyric acid heptyl ester

D,L N— benzenesulfonyl-3-aminobutyric acid propyl ester

D,L N-benzoyl-3-aminobutyric acid 2-propenyl ester

D,L N-4-methylbenzoyl-3-aminobutyric acid 1-methylhexyl ester

D,L N-4-methylbenzoyl-3-aminobutyric acid 1-methyldecanyl ester

D,L N-3,4-dimethylbezoyl-3-aminobutyric acid heptyl ester

D,L N-4-methylbezoyl-3-aminobutyric acid 1-methylpentyl ester

D,L N-2-methylaminobenzoyl-3-aminobutyric acid methyl ester.

D,L N-4-chlorobenzensulfonyl-3-aminobutyric acid 1-methylpentyl ester

D,L N-benzensulphonyl-3-aminobutyric acid 3-phenylpropyl ester

D,L N-2-methylaminobenzoyl-3-aminobutyric acid 1-methylpentyl ester

D,L N-benzensulfonyl-3-aminobutyric acid 3,5-dichlorophenyl ester

D,L N-4-2-thiophenebenzoyl-3-aminobutyric acid octyl ester

D,L N-4-2-thiophenebenzoyl-3-aminobutyric acid 1-methylpentyl ester

D,L N-3,4-dimethylbenzoyl-3-aminobutyric acid octyl ester

Production methods

The novel compounds encompassed by the present application arestructurally related to known compounds and can be easily prepared byeither derivatising the known compounds or by modifying the proceduresfor preparing the known compound, as required. These procedures will beapparent to those skilled in the art. The following procedures areillustrative.

Compounds of the formula (I)

wherein R₁ and R₂ and R₄ are as previously defined and R₃ representshydorgen or C₁₋₈ alkyl can be obtained from β-aminobutyric acid.

To prepare compounds of formula (I) where R₆ and R₇ are as previouslydefined β-aminobutyric acid is reacted with NR₇H₂, wherein R₇ is aspreviously defined. Reactions of this type are described in theliterature, e.g., by A. Zilkha and J. Rivilin, J. Org. Chem. 1957, 23,94.

The present compounds were found to be effective against late blight inpotato and tomatoes, powdery mildew in cereals, downy meldow incucumber, melon and grapes.

The present compounds of this invention will typically be applied tocrops or their locus before or after the onset or after the initialsigns of fungal attack and may be applied to the foliar surfaces of thecrop. The amount of active ingredient to be employed will be sufficientto induce the systemic resistance of the crop to control the fungi andwill vary depending on such factors as the species of fungi to becontrolled, the type of treatment (for example, spraying dusting, seedtreatment, soil drench), the condition of the crop, and the particularactive ingredient used.

As an application to the crop or its locus, the compounds will beapplied to the crops with a dosage rate of from 0.1 to 5 kg/ha,preferably from 0.2 to 2 kg/ha. with application being repeated asnecessary, typically at intervals of every one to three weeks.

Depending on circumstances, the compounds of this invention may be usedin association with other pesticides, e.g., fungicides, insecticides,acaricides, herbicides, or plant growth regulating agents in order toenhance their activity or to widen their spectrum of activity.

The compounds of this invention are conveniently employed as fungicidalcomposition in association with agriculturally acceptable carriers ordiluents. Such compositions also form part of the present invention.They may contain, aside from a compound of formula (I) as active agent,other active agents, such as fungicides. They may be employed in eithersolid or liquid application forms e.g., in the form of a wettablepowder, an emulsion concentrate, a water dispersible suspensionconcentrate (“flowable”), a dusting powder, a granulate, a delayedrelease form incorporating conventional carriers, diluents and/oradjuvants. Such compositions may be produced in conventional manner,e.g. by mixing the active ingredient with a carrier and otherformulating ingredients.

Particular formulations to be applied in spraying forms such as waterdispersible concentrates or wettable powders may contain surfactant suchas wetting and dispersing agents, e.g., the condensation product offormandehyde with naphthalene sulphonate, an alkyl-aryl-sulphonate, alignin sulphonate, a fatty alkyl sulphate an ethoxylated alkylphenol andan ethoxylated fatty alcohol.

In general, the formulations include from 0.01 to 90% by weight ofactive agent, said active agent consisting either of at least onecompound of formula (I) or mixture thereof with other active agents,such as fungicides. Concentrated forms of compositions generally containbetween about 2 and 80%, preferably between about 5 and 70% by weight ofactive agent. Application forms of formulation may, for example, containfrom 0.01% to 20% by weight, preferably from 0.01% to%5 by weight, ofactive agent.

Formulation Example I: Wettable powder

50 parts by weight of a compound of formula (I) are ground with 2 partsof lauryl sulphate, 3 parts sodium lignin the sulphonate and 45 parts offinely divided kaolininite until the mean particle size is below 5microns. The resulting wettable powder so obtained is diluted with waterbefore use to a concentration of between 0.01% to 5% active ingredient.The resulting spray liquor may be applied by foliar spray as well as byroot drench application.

Formulation Example II: emulsion concentrate

25 parts by weight of a compound of formula I, 65 parts of xylene, 10parts of the mixed reaction product of an alkylphenol with xyleneoxideand calcium-dodecyl-benzene sulphonated are thoroughly mixed until ahomogeneous solution is obtained. The resulting emulsion concentrate isdiluted with water before use.

Formulation Example III: Granulate (for soil treatments)

Onto 94.5 parts by weight of quartz sand in a tumbler mixer is sprayed0.5 parts by weight of a binder (non-ionic tenside) and is thoroughlymixed. 5 parts by weight of compound of the formula (I) in powdered formare then added and thoroughly mixed to obtain a granulated formulationwith a particle size in the range of from about 0.3 to about 0.7 mm. Thegranulate may be applied by incorporation into the soil adjacent theplants to be tested.

Formulation Example IV: Seed or Tuber Dressing

25 parts by weight of compound of the formula (I), 15 parts ofdialkylphenoxy-poly-(ethylenoxy) ethanol, 15 parts of fine silica, 44parts of fine kaolin, 0.5 parts of a colorant (e.g., crystal violet) and0.5 pars of xantham gum are mixed and ground a contraplex mill atapproximately 10,000 rpm to an average particle size of below 20 micron.

The resulting formulation is applied to the seeds or tubers as anaqueous suspension in an apparatus suitable for that purpose. Where thecompound of the formula (I) is liquid, it is first absorbed on thecarriers, if desired with the aid of a small amount of a volatilesolvent such as acetone. The resulting powder if first allowed to dry ifa solvent is used, then the other ingredients are added and the rest ofthe procedure is carried out.

Formulation Example V: Soil Drench Drip Irrigation

2 parts by weight of compound of the formula (I) are dissolved in 1,000parts of water. The resulting formulation is applied to plant by dripirrigation.

As previously mentioned, the compounds of formula (I) are effective inactivation or enhancing a corp's defense system against fungal diseasescaused by fungi. Such activity can be demonstrated in usign the generalprocedures of the following tests:

while the invention will now be described in connection with certainpreferred embodiments in the following examples, it will be understoodthat it is not intended to limit the invention to these particularembodiments. On the contrary, it is intended to cover all alternatives,modifiations and equivalents as may be included within the scope of theinvention as defined by the appended claims. Thus, the followingexamples, which include preferred embodiments, will serve to illustratethe practice of this invention, it being understood that the particularsshown are by way of example and for purpses of illustrative discussionof preferred embodiments of the present invention only and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of procedures, as well as of theprinciples and conceptual aspects of the invention.

EXAMPLES Example 1

D,L-N-benzenesulfonyl-3-amino N-benzyl butyramide

To 6.0 gr β-Aminobutyric acid in 20 ml water was added 5.4 gr NaOHdissolved in 26 ml water. 10.3 gr Benzenesulfonyl chloride in 36 mlDichloroethane was added at r.t. during 15 minutes. The mixture wasstirred for 10 minutes at r.t. and heated at 68° C. during 4 hr. Thephases were separated, and the aqueous one, was acidified with HCl(conc) to pH 2.5. After extrcation with Dichloroethane (DCE)DL-N-benzenesulfonyl-3 aminobutyric acid (I) crystallized from theorganic phase. 6.7 gr m.p. 125-127. 4° C.

To 7.7 gr compound I, in 80 ml Dichloroethane, was added 7.5 gr PCl₅ insmall portions, keeping the mixture temperature at 5° C. The mixture wasallowed to warm to r.t. and stirred during 6 hr. Petrol ether 60-80 (400ml) was added, the chloride was filtered and dried yielding 7.3 grproduct (II).

To 3.0 gr of the acid chloride (II) in 30 ml DCE, was added 2.3 grbenzylamine in 5 ml DCE during 10 minutes at 10-15° C. The mixture washeated to 50° C. during 7 hr. 30 ml of water was added, the organicpahse separtated, and after concentration of the solution the productprecipitated. 2.66 gr m.p. 105-107° C. NMR and MS spectrocopic methodsconfirmed the structure.

Example 2

D,L-N-benzensulfonyl-3-aminobutyranilide

To 3.0 gr Acid chloride (II) in 30 ml DCE was added 2.0 gr aniline in 5ml DCE during 10 minutes at 10-15° C. The mixture was heated at 50° C.during 7 hr. 30 ml of water was added, and the organic phase wasseparated. Evaportaion of the solvent gave 3.5 gr product.Recrystallization from toluene gave 2.7 gr mp. 130-132° C. NM and MSspectroscopic methods confirmed the structure.

Example 3

D,L-N-β-methyl benzoyl-3-aminobutyric acid n-octyl ester

To 2.0 gr β-Aminobutyric acid in 9 ml water, was added 3.4 gr NaOH in 9ml water. 3.0 gr of β-Toluoyl chloride in 15 ml DCE was added during 20minutes at r.t. The mixture was heated at 62° C. during 7 hr. The phaseswere separated, and the aqueous one was acidified with HCl (conc) to pH2.0-2.5. The compound precipitated; decantation and recrystallizationwith water gave after trituration with DCE, 3.3 gr. m.p. 115-118° C., ofD,L-β-methylbenzoyl-3-aminobutyric acid (III). to 3.0 gr of the acid(III) in 35 ml DCE, was added 3.2. gr PCl₅ in small portions, keepingthe mixture temperature at 10-15° C. The mixture was allowed to warm to25° C. and was stirred for 7 hr. Petrol ether 60-80 (280 ml) was addedand oil was separted. Decantation of the solvent and addition of 50 mlPetrol ether gives a crystaline compound. After filtration we obtain 2.5gr acid chloride IV.

To the chloride IV in 25 ml DCE was added 4.1 gr n-octanol in 5 ml DCEduring 20 minutes at 30° C. The mixture was heated at 65° C. during 6hr. Afte distillation, 25 ml DCE was added, washed with 3×10 ml sodiumbicarbonate 2% and dired over MgSO₄. Evaporation of the solvent gave 2.1gr m.p. 41-42° C. of the product. NMR and MS confirmed the structure.

Example 4

N-β-methyl benzoyl-3 aminobutyric acid-sec. butyl ester

Method A

To 2.6 gr chloride IV in 25 ml DCE, was added 2.3 gr 2-butanol in 5 mlDCE, during 10 minutes at 25° C. The mixture was heated at 65° C. during6 hr. After distillation, 25 ml DCE was added, washed with sodiumcicarbonate 2% and dried over MgSO₄, Evaporation of the solvent gave 2.2gr of the product. NM and MS spectroscopic methods confirms thestructure.

Method B

The mixture of 2.0 gr D,L-β-methylbenzoyl-3-aminobutyric (III) 0.85 gr2-butanol, 30 ml Toluene and 0.04 gr H₂SO₄ (conc) was heated underreflux for ca 7 hr. The water formed in the reaction was separated byazeotropic distillation. The cooled reaction mixture was washed twicewith 15 ml water, sodium bicarbonate 2% and dried over MgSO₄.Distillation of the solvent yield 1.7 gr of the ester.

Example 5

D,L-N-3-4-dichlorobenzoyl-3-amino butyric acid n-octyl-ester

D,L-N-3,4-dichlorobenzoyl-3-aminobutyric acid n-octyl ester

To 1.5 gr β-Aminobutyric acid in 5 ml water, was added 2.5 gr NaOH in6.4. ml water. 3.0 gr of 3,4-dichloro benzoyl chloride in 10 ml DCE wasadded during 10 minutes at r.t. The mixture was heated at 65° C. during6.5 hr. The phases were separated. The aqueous phase was washed twicewith 15 ml DCE and acidified with HCl (conc) to pH 1.5-2.0. The compoundwas filtered. 3.1 gr mp 143-146° C. (V) were obtained.

To 2.5 gr compound V in 35 ml dichloroethane (DCE), was added 2.2 grPCl₅ in small portions, keeping the mixture temperature at 10-15° C. Themixture was allowed to warm to 25° C., and stirred for 7 hr. Petrolether 60-80 was added, the acid chloride precipitated, filtered anddried, yielding 1.5 gr.

To the chloride in 25 ml DCE was added 2.0 gr n-octanol in 5 ml DCEduring 10 minutes at 20° C. The mixture was heated at 65° C. during 7hr. After distillation, 25 ml DCE was added, washed with sodiumbicarbonate 2% and dried over MgSO₄. Evaporation of the solvent gave 2.0gr of the titled compound. NMR and MS spectroscopic methods confirmedthe sturcture.

Example 6

D,L-N-4-chlorobenzoyl-3-aminobutyric acid 2-chloro-ethyl ester

D,L-N-4-chlorobenzoyl-3-aminobutyric acid-2-chloro-ethyl ester

To 3.0 gr β-Aminobutyric acid in 7 ml water, was added 3.4 gr NaOH in8.7 ml water. 3.1 gr of β-chlorobenzoyl chloride in 15 ml DCE was addedduring 15 minutes at 10-15° C. The mixture was heated at 60° C. during 7hr. The phases were separated, and the aqueous phase was washed twicewith 15 ml DCE, and acidified with HCl (conc) to pH 1.5-2.0. Thecompound was filtered and recristallized with water. 3.94 gr ofDL-β-Chlorobenzoyl-3 aminobutyric acid (VI) was obtained.

To 3.0 gr of acid VI in 25 ml Dce, was added 2.93 gr PCl in smallportions, keeping the mixture temperature at 8-10° C. The mixture wasallowed to warm to 25-27° C. and stirred for 7 hr. Petrol ether 60-80(150 ml) was added, the chloride was filtered and dried yielding 2.7 gr(VII).

To 2.5 gr of acid chloride VII in 20 ml DCE was added 2-chloroethanol in5.0 ml DCE during 10 minutes at 15-17° C. The mixture was heated at 65°C. during 7 hr. After distillation 35 ml DCE was added, and washed withsodium bicarbonate 2%. Evaporation of the solvent gave 1.73 gr product.Crystallization from cyclohexane yield 0.5 gr. mp 80-81° C. NMR and MSspectroscopic methods confirmed the sturcture.

Example 7

DL-N-benzenesulfonyl-3-aminobutyric acid n-octyl ester

DL-N-benzenesulfonyl-3-aminobutyric acid n-octyl ester

The mixture of 2.0 gr DL-N benzensulfonyl-3 aminobutyric acid (I), 1.78gr n-octanol, 30 ml Toluene and 0.04 gr H₂SO₄ (conc) was heated underrefulux for ca 3 hr. The water formed in the reaction was separated byazeotropic distillation. The cooled reaction mixture was washed twicewith bicarbonate 2%, and dried over magnesium sulfate. Distillation ofthe solvent and alcohol yield 2.0 gr product, confirmed by spectroscopy.

Example 8

N-benzenesulfonyl-3-aminobutyric acid-sec butyl ester

N-benzenesulfonyl-3-aminobutyric acid-sec butyl ester

The mixture of 2.0 gr DL-N benzensulfonyl-3 aminobutyric acid (I), 1.0gr 2-butanol, 30 ml toluene and 0.04 gr H₂SO₄ (conc) was heated underreflux for ca 6 hr. The water formed in the reaction was separated byazeotropic distillation. The cooled reaction mixture was washed twicewith bicarbonate 2%, and dried over magnesium sulfate. Distillation ofthe solvent and alcohol yield 1.8 gr procuct, confirmed by spectroscopy.

Example 9

N-benzenesulfonyl-3-aminobutyric acid 1-methyl-1-butyl ester

N-benzenesulfonyl-3-aminobutyric acid 1-methyl-1-butyl ester

The mixture of 2.0 gr DL-N benzensulfonyl-3 aminobutyric acid (I), 1.2gr 2-Pentanol, 30 ml toluene and 0.04 gr H₂SO₄ (conc) was heated underreflux for ca 6 hr. The reaction was treated as in the previous example.2.0 gr of the ester was obtained, confirmed by spectroscopy.

Example 10

N-β-methylbenzoyl-1-aminobutyric acid-1-methyl-1-pentyl ester

N-β-methylbenzoyl-1-aminobutyric acid-1-methyl-1-pentyl ester

The mixture of 2.0 gr DL-p methylbenzoyl-3 aminobutyric acid (III), 1.6gr 2-hexanol, 30 ml toluene and 0.04 gr H₂SO₄ (conc) was heated underreflux for ca 7 hr. The water formed in the reaction was separated byazeotropic distillation. The cooled reaction mixture was washed with3×15 ml water, 2×15 ml bicarbonate 2% and dried over MgSO₄. Afterdistillation of solvent and alcohol 2.2 gr of the ester was obtained,confirmed by spectorscopy.

Example 11

DL-N-benzoyl-3-aminobutyric acid 2-chloroethyl ester

DL-N-benzoyl-3-aminobutyric acid 2-chloroethyl ester

To 1.68 gr DL-N-benzoyl-3-aminobutyric acid chloride, prepared in ananalogous way as the acid chloride VII (Example 6), in 25 ml DCE wasadded 2.5 gr 2-chloroethanol in 5 ml DCE during 10 minutes, at 19-20° C.The mixture was heated at 65-67° C. for ca 7 hr. After distillation ofthe solvent and alcohol, 20 ml of DCE was added, an washed with 2%bicarbonate. Evaporation of the solvent yield 1.4 gr product, confirmedby spectroscopy.

Example 12

N-benzenesulfonyl-3-aminobutyric acid-1 methyl 2-methoxy ethyl ester.

To 6.0 gr of β-Aminobutyric acid in 20 ml water, was added 5.4 gr ofNaOH dissolved in 26 ml water. 10.3 gr of benzensulfonyl chloride in 36ml dichloroethane was added at r.t. during 15 minutes. The mixture wasstirred 10 minutes at r.t. and heated at 68° C. during 4 hr. The phaseswere separated, and the aqueous one, was acidified with HCI (conc) to pH2.5. After the extraction with dichloroethane,n-benzenesulfonyl-3-aminobutyric acid crystallized from the organicphase. 6.7 gr m.p. 125-127.4° C. to 7.7 gr ofn-benzenesulfonyl-3-aminobutyric acid in 80 ml DCE, was added 7.5 gr insmall portions, keeping the mixture temperatured at 5° C. The mixturewas allowed to warm to r.t. and stirred during 6 hr. Petrol ether 60-80(400 ml) was added, the chloride was filter and dried yielding 7.3 gr ofthe acid chloride. The 2.0 gr of the acid chloride in 30 ml DCE wasadded 1-methoxy-2-propanol dissolved in 5 ml DCE at 10-15° C. Themixture was heated at 63-65° C. during 6.5 hr. The reaction was washedtwice with 20 ml water and sodium bicarbonate 2% and dried over MgSO₄and Distillation of the solvent and excess alcohol yield 1.75% of theproduct. The structure was confirmed by MS and NMR spectroscopicmethods. By proceeding as described above, using the suitable startingmaterials compounds 19,29,31,36 and 47 were prepared.

Example 13

N-2-methylaminobenzoyl-3-aminobutyric acid methyl ester.

The mixture of 17.7 gr N-methylisatoic anhydride, 10.3 gr β-Aminobutyricacid, 1.5 gr triethylamine and 150 n Toluene, was refluxed during 7 hr.The solids were removed by filtration andN-2-methylaminobenzoyl-3-aminobutyric acid crystallized from thefiltrate. The compound was filtered and washed with water and toluenewhere 5.4 gr were obtained. To 2.0 gr ofN-2-methylaminobenzoyl-3-aminobutyric acid in 19 gr methanol, 2,3 gr ofthionyl chloride was added at r.t. The mixture was heated to 60° C.during 6.5 hr. After the distillation of methanol, 50 ml Dichloroethanewas added. The solution was washed twice with 25 ml sodium bicarbonate2%, 25 ml water and dried over MgSO₄. After the evaporation of thesolvent, 1.8 gr product was obtained. NMR and MS spectroscopic methodsconfirmed the structure.

Example 14

N-4-methoxy-benzoyl-3-aminobutyric acid n-heptyl ester.

To 9.2 gr β-aminobutyric acid in 32 ml water, was added 15.6 gr of NaONin 40 ml water. 16.6 gr of 4-methoxybenzoylchloride in 60 mlDichloroethane (DCE) was added during 20 minutes at 15-20° C. Themixture was heated at 65° C. during 7.5 hr. The phases were separated,and the aqueous one was acidified with HCl (conc) to pH 2-2.5. Thecompound precipitated. 18.7 gr of n-4-methoxy-benzoyl-3-aminobutyricacid was obtained m.p. 112-116 after recrystallization with DCE. Themixture of 2.0 gr n4-methoxy-benzoyl-3-aminobutyric acid, 1.6 gr1-heptanol, 30 ml Toluene and 0.04 gr H₂SO₄(conc) was heated underreflux for 7 hr. The water formed in the reaction was separated by azeotropic distillation. The cooled reaction was washed twice with 25 mlwater. After the evaporation of the solvent, the excess alcohol wasdistilled at 90° C. (0.4 mm Hg) and 0.8 gr product was obtained. NMR andMS spectroscopic methods confirmed the sturcture.

Example 15

N-benzoyl-aminobutyric acid-cyclohexyl ester.

The mixture of 2.0 gr n-benzoyl-3-aminobutyric acid, 1.6 grcyclohexanol, 30 ml toluene and 0.04 gr H₂SO₄ (conc) was heated underreflux during 2 hr, the water formed in the reaction was separated byazeotropic distillation. The cooled solution was washed with water andtwice with 30 ml 2% sodium bicarbonate. After the evaporation of thesolvent, and distillation of the excess alcohol at 50° C., 0.4 mmHg,1.5% oily product, which soldified, was obtained. m.p. 60-63° C. Thesturcture was confirmed by MS and NMR spectoroscopic methods.

Example 16

N-benzoyl-3-aminobutyric acid-2 propenyl ester (compound 42)

The mixture of 10 gr n-benzoyl-3-aminobutyric acid 4.8 gr allylalcohol,70 ml toluene and 0.2 gr H₂SO₄ (conc) was heated under reflux during 7hr. The water formed in the reaction was separated by azeotropicdistillation. The solution was washed with water, 2% sodium bicarbonateand dried over MgSO₄ After the distillation of the solvent 5.0% of theproduct was obtained. MS and NMR spectroscopic methods approved thesturcture.

Compounds 12-18, 20-28, 30-35,37-46 and 48 were prepared by similarmanners to those described in examples 13-16 using suitable startingmaterials.

I. Activity against late blight in potato and tomato.

For the following experiments we have used six weeks old potted potatoplants (Solanum tuberosum cultivar Alpha) or 4-weeks old potted tomatoplants (Lycopersicon esculentum cultivar Florida basket). Plants weresprayed with the test compound and two days later were challengeinoculatedd with the lated blight fungus Phytophthora infestans.

Inoculation was carried out as follows:

1. The fungus was grown on potato tuber slices at 15° C. for 7 days.

2. Sporaganic produced on tuber slices were harvested into cold (4° C.)distilled water and their concentration adjusted to 2.5-3×10³sporaganic/ml.

3. Sporangical suspension was sprayed to run off onto the treatedplants. Untreated plants were also inoculated as controls.

4. Inoculated plants were placed in a dew chamber at 18° C. for 20 hrand then transferred into a growth chamber at 20° C. with 12 hr lighrphotoperiod and 60-70% RH.

5. At 4-7 days post inoculation the intensity of disease developed wasvisually activated by assessing the percentage of the foliage areakilled by the fungus.

6. Control efficacy achieved by the spray treatment was calculatedrelative to the disease intensity seen on the control plants. Forexample when % foliage area killed was 90% in the control plants and 10%in the treated plants, control efficancy was calculated as${\left( {1 - \frac{10}{90}} \right)\quad \cdot 100} = {88.0\%}$

Results are shown in Tables 1 and 2.

TABLE 1 Activity of some BABA Derivatives against late blight caused byPhytophthora infestans in potato and tomato. Control Efficacy % PotatoTomato Com- 26.7.96 17.7.096 14.8.96 12.7.96 14.8/96 pounds (ppm) (ppm)(ppm) (ppm) (ppm) from 500 2000 500 2000 2000 500 2000 2000 Example 1 4979 57 77 72 82 97 90 Example 2 42 68 45 81 74 85 85 83 Example 6 — — 7550 88 76 79 67 Example 3 85 92 70 81 88 — 70 93 Example 4 23 42 56 75 77— 85 90

TABLE 2 Activity of some BABA derivatives against late blight cause byPhytophthora infestans in potato, 3-8 days after inoculation. Dose: 2000ppm Control efficacy % Compounds from 3 days 4 days 6 days 8 daysExample 7 100 100 82 77 Example 8 100 92 87 50 Example 9 99 97 82 62Example 10 100 100 97 87 Example 11 95 92 82 70

Experimental

Late blight in potato caused by Phytophthora infestans, additionalexamples

Potato plants (cv.Alpha) were raised from tubers in 1 liter pots in thegreenhouse. At 4 weeks after “sowing” when had 3-4 shoots with 10-12leaves, plants were sprayed with test solutions onto their adaxialsurfaces and incubated at 20° C. growth cabinets. Two days after sprayplants were inoculated with sporangial suspension (2000 sporangia/ml) ofP.infestans (A2 mating type, resistant to metalaxyl). Inoculated plantswere placed in 100% relative humidity in the dark for 20 hours and thenreturned to a 20° C. growth cabined for symptom production. Percentageleaf area covered with blight symptoms was visually assessed 6 daysafter inoculation. Control efficacy was calculated relative to thecontrol inoculated plants. The results are shown in Table 3.

TABLE 3 Activity of some additional BABA derivatives against late blightcaused by Pytophtora infestans in Potato 6 days after inoculation. Dose:500 ppm CH₃C(H)NHR₇CH₂C(O)—OR₃ Control efficacy (%) Compd. R₇ R₃ 6d 124-CH₃OC₆H₄CO (CH₂)₆CH₃ 89 13 6,5-(CH₆)₂C₆H₆CO (CH₂)₆CH₃ 84 48 2-C₄H₃SCO(CH2)7CH3 82 14 2,6-F₂C₆H₆CO (CH₂)₆CH₃ 79 15 4-C(CH₆)₆C₆H₄CO (CH₂)₆CH₃79 16 4-CH₆C₆H₄SO₂ CH(CH₆)(CH₂)₆CH₃ 79 50 4-ClC₆H₅SO₂ CH(CH₃)(CH₂)₃CH₃77 17 C₆H₅SO₂ (CH₂)₃C₆H₅ 76 18 4-ClC₆H₄CO CH(CH₃)(CH₂)₃CH₃ 76 51 C₆H₅SO₂(CH₂)₃C6H5 76 49 2-C₄H₃SCO CH(CH₃)(CH₂)₃CH₃ 75 19 C₆H₅SO₂ CH₂CCl₃ 75 204-CH₆C₆H₄SO₂ CH(CH₃)CH₂CH₃ 75 52 2-CH₃NHC₆H₄CO CH(CH₃)(CH₂)₃CH₃ 74 213,4diCH₆C₆H₆CO CH(CH₃)(CH₂)₂CH₃ 73 22 3-CH₆C₆H₄CO (CH₂)₆CH₃ 70

Late blight in tomato caused by Phytophthora infestans

Tomato plants (cv.baby) were raised from seed in 0.2 liter pots in thegreenhouse. At 3 weeks after sowing when had 6 leaves plants weresprayed with the test solution onto their adaxial surfaces. They wereinoculated and further handled and assessed for disease development asdescribed in Section 1 above. The results are shown in Table 4.

TABLE 4 Activity of some BABA derivatives against late blight caused byPytophtora infestans in Tomato, 7 days after inoculation. Dose: 500 ppmCH₃C(H)NHR₇CH₂C(O)—OR₃ Control efficacy % Compd. R₇ R₃ 7d 35 ClC₆h₅SO₂CH₂CH₂CH₃ 81 36 4-CH₃C₆H₄CO CH₂CCl₃ 81 37 4-CH₃C₆H₄CO cyclohexyl 78 38C₆H₅CO cyclohexyl 78 39 C₆H₅SO₂ cyclohexyl 75 52 2-CH₃NHC₆H₄COCH(CH₃)(CH₂)₃CH₃ 75

II. Activity against powdery mildew in cereals

For the following experiments we have used 10-days old potted wheatplants (Triticum asetivum cultivar Atir) and barley plants (Hhordeumvulgaris cultivar Amidon).

Plants were sprayed with the test compounds and two days lated wereinoculated with the powdery mildew fungal pathogens. Wheat wasinoculated with Erysiphe granims tritici. Barley was inoculated with thepowdery Erysiphe granims hordei.

Inoculation was done by shaking infected donor plants harboring abundantconidia over the treated plants. Untreated plants were also inoculatedas controls. Inoculated plants were placed in a growth chamber at 20-22Cwith 1 rhr photoperioed and 50-60% RH. At 9-10 days after inoculationdisease intesity was visually assessed by estimating the percentage leafarea occupied by fungal colonies.

Control efficacy of the disease achieved by the sprayed test compoundwas calculated relative to the amount of disease seen in the control.For example when% foliage area occupied by fungal colonies was 90%treated plants, control efficacy was calculated as${\left( {1 - \frac{10}{90}} \right)\quad \cdot 100} = {88.9\%}$

Results are shown in Table 5

TABLE 5 Activity of some BABA derivatives against powdery mildew causedby Erysiphe graminis in cereals. Control Efficacy % Barley 17.9.96 Wheat7.8.96 Compound from 500 2000 500 2000 Example 1 25 75 — — Example 6 6275 — — Example 4 87 95 96 96 Example 5 82 85 76 92

Powdery mildew in wheat caused by Erysiphe grarinis tritici, additionalexamples.

Wheat plants (cv.Shafir) were raised from seed in the greenhouse, 30plants per 0.2 liter pot. When the first leaf was fully developed plantswere sprayed with the test solutions and placed in a 20° C. growthcabinet. Two days after spraying plants were dusted with conidia of E.graminis tritict so that about 100 spores were settled on 1 cm² of leafarea (both surfaces). Inoculated plants were placed in a 20° C. growthcabinet for 7 days until number of fungal colonies per plant werecounted. Control efficacy was calculated relative to number of coloniesdeveloped on the control-inoculated untreated plants. The results areshown in Table 6.

TABLE 6 Activity of some BABA derivatives against powdery mildew causedby Erysiphe graminis in wheat 7 days after inoculation. Dose: 500 ppmCH₃C(H)NHR₇CH₂C(O)—OR₃ Control efficacy (%) Compd. R₇ R₃ 7d 38 C₆H₅COCyclohexyl 100 53 C₆H₅SO₂ 3,5-(Cl)₂C₆H₃ 100 50 4-ClC₆H₄SO₂CH(CH₃)(CH₂)₃CH₃ 92 12 4-CH₃OC₆H₄CO (CH₂)₆CH₃ 85 32 2-CH₃C₆H₄CO(CH₂)₆CH₃ 83 16 4-CH₃C₆H₄SO₂ CH(CH₃)(CH₂)₃CH₃ 83 35 4-ClC₆H₅SO₂CH₂CH₂CH₃ 81 47 2-CH₃NHC₆H₄CO CH₃ 81 41 C₆H₅SO₂ CH₂CH₂CH₃ 77 42 C₆H₅COCH₂CH═CH₂ 77 43 4-CH₃C₆H₄CO CH(CH₃)(CH₂)₄CH₃ 75 44 4-CH₃C₆H₄COCH(CH₃)(CH₂)₅CH₃ 74 15 4-C(CH₃)₃C₆H₄CO (CH₂)₆CH₃ 74 13 3,5-C(CH₃)₂C₆H₅CO(CH₂)₆CH₃ 72 45 3,4 diCH₃C₆H₃CO (CH₂)₆CH₃ 71 46 4-CH₃C₆H₄COCH(CH₃)(CH₂)₃CH₃ 69 54 3,4-(CH₃)₂C₆H₃CO (CH₂)₇CH₃ 69

III. Downy mildew in cumber and melon caused by Pseudoperonosporacubensis

Cucumber plants (cv,Dlila) and melon plants (cv.Ein Dor) were raisedfrom seeds in 0.2 liter pots in the greenhouse. At 3 weeks after sowingwhen had 3 true leaves they were inoculated with sporangial suspension(1000 sporangia/ml) of P.cubensis (resistant to metalaxyl) and placed in100% relative humidity in the dark for 20 hr. They were then place in a20° C. growth cabinet for 7 days and assessed for disease development.Percentage leaf area covered with disease symptoms was evaluated andcontrol efficacy was calculated relative to control inoculated plants.The results are shown in Tables 7 and 8.

TABLE 7 Activity of some BABA derivatives against downy mildew caused byPseudoperonospora cubesis in melon, 7 days after inoculation. Dose: 500ppm CH₃C(H)NHR₇CH₂C(O)—OR₃ Control efficacy % Compd. R₇ R₃ 7 days 124-CH₃OC₆H₄CO (CH₂)₆CH₃ 100 15 4-C(CH₃)₃C₆H₄CO (CH₂)₆CH₃ 97 17 C₆H₅SO₂(CH₂)₃C₆H₅ 87 18 4-ClC₆H₄CO CH(CH₃)(CH₂)₃CH₃ 87 51 C₆H₅SO₂ (CH₂)₃C₆H₅ 8722 3-CH₃C₆H₄CO (CH₂)₆CH₃ 83 19 C₆H₅SO₂ CH₂CCl₃ 83 25 3,4Cl₂C₆H₃COCH(CH₃)(CH₂)₃CH₃ 80 32 2-CH₃C₆H₄CO (CH₂)₆CH₃ 77 33 4-CH₃C₆H₄SO CH₂CH₂Br75 27 3,5-(CH₃)₂C₆H₃CO CH₂CH₂Cl 73 23 3,5-(CH₃)₂C₆H₃CO CH(CH₃)(CH₂)₃CH₃73 34 4-CH₃C₆H₄SO₂ (CH₂)₆CH₃ 70 29 C₆H₅CO CH₂CCl₃ 70

TABLE 8 Activity of some BABA derivatives against dony mildew caused byPseudoperonospora cubesis in cucumber, 7 days after inoculation. Dose:500 ppm CH₃C(H)NHR₇CH₂C(O)—OR₃ Control efficacy (%) Compd. R₇ R₃ 7d 522-CH₃NHC₆H₄CO CH(CH₃)(CH₂)₃CH₃ 97 40 ClC₆H₅SO₂ (CH₂)₆CH₃ 82 364-CH₃C₆H₄CO CH₂CCl₃ 82 38 C₆H₅CO Cyclohexyl 80 35 ClC₆H₅SO₂ CH₂CH₂CH₃ 7737 4-CH₃C₆H₄CO Cyclohexyl 75 39 C₆H₅SO₂ Cyclohexyl 70

IV. Downy mildew in grapes caused by Plasmoparavlticola

Grape plants (cv.Superior) were raised from cuttings and when developed5-6 expanded leaves they were sprayed with the test solutions on theirabaxial (lower) leaf surfaces. Two days after spraying plants wereinoculated with sporangial suspension of P.viticola (104 sporangia/ml)onto their lower leaf surface and placed in 100% relative humidity for20 hr. The plants were then placed in a growth cabinets 20° C. for 10days. Disease development was assessed according to the abaxial leafsurfaces area covered with fungal sporulation. Fungal sporulation wasinduced by placing the infected plants in 100% relative humidity in thedark for 48 hr. The results are shown in Table 9.

TABLE 9 Activity of some BABA derivatives against downy mildew caused byPeronospora viticola in Grapes, 10 days after inoculation. Dose: 500 ppmCH₃C(H)NHR₇CH₂C(O)—OR₃ Control efficacy % Compd. R₇ R₃ 10d 164-CH₃C₆H₄SO₂ CH(CH₃)(CH₂)₃CH₃ 100 14 2,6-F₂C₆H₃CO (CH₂)₆CH₃ 100 233,5-(CH₃)₂C₆H₃CO CH(CH₃)(CH₂)₃CH₃ 100 20 4-CH₃C₆H₄SO₂ CH(CH₃)CH₂CH₃ 10024 3,4Cl₂C₆H₃CO (CH₂)₆CH₃ 100 25 3,4Cl₂C₆H₃CO CH(CH₃)(CH₂)₃CH₃ 100 264-CH₃C₆H₄CO (CH₂)₃C₆H₅ 99 15 4-C(CH₃)₃C₆H₄CO (CH₂)₆CH₃ 97 273,5-(CH₃)₂C₆H₃CO CH₂CH₂Cl 97 17 C₆H₅SO₂ (CH₂)₃C₆H₅ 97 51 C₆H₅SO₂(CH₂)₃C₆H₅ 97 19 C₆H₅SO₂ CH₂CCl₃ 94 28 4-CH₃OC₆H₄CO CH₂CH₂Cl 91 29C₆H₅CO CH₂CCl₃ 91 30 4-ClC₆H₄CO (CH₂)₆CH₃) 91 18 4-ClC₆H₄COCH(CH₃)(CH₂)₃CH₃ 91 31 C₆H₅SO₂ CH(CH₃)CH₂OCH₃ 82

What is claimed:
 1. A compound having the formula (I)

Wherein: a) R₁ and R₂ are independently hydrogen, C₁₋₈ alkyl, phenyl,and phenyl C₁₋₄ alkyl b) R₃ is C₁₋₂₃ straight or branched or a cyclicalkyl or alkenyl; alkoxyalkyl halogenated alkyl, phenyl, or benzyl;alkyl phenyl; c) R₄ and R₅ are hydrogen or C₁₋₈ alkyl where at least oneof R₄ and R₅ is C₁₋₈ alkyl; d) R₆ is hydrogen; C₁₋₈ alkyl; C₂₋₈alkanoyl; phenyl C₁₋₄ alkyl, benzoyl wherein the phenyl moiety isoptionally substituted by one or more halogen atoms or alkyl groups C₂₋₈alkoxycarbonyl; CONHR₈ wherein R₈ is hydrogen, C₁₋₈ alkyl, phenyl,phenyl C₁₋₄ alkyl; phenyl C₂₋₄ alkoxycarbonyl; e) R₇ is benzenesulfonylor benzoyl optionally substituted by one or more halogens, alkyl groups,amino groups or alkoxy groups; or thiophene carbonyl; f) X is O or NH;and salts thereof; with the proviso that when X is oxygen, R₁ ishydrogen and R₂ is ethyl, then R₃ is neither methyl nor ethyl; and whenX is oxygen, R₂ is hydrogen and R₃ is methyl, then R₁ is not ethyl.
 2. Acompound according to claim 1, wherein R₁ and R₂ are independentlyhydrogen, R₃ is C₁₋₂₃ straight or branched or a cyclic alkyl or alkenyl;alkoxyalkyli halogenated alkyl, phenyl, or benzyl; alkyl phenyl; R₄ andR₅ are independently hydrogen or C₁₋₃ alkyl; R₆ is hydrogen: R₇ isbenzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl; and X is oxygen or —NH.
 3. A compound according to claim 1,wherein R₁, R₂, R₅, and R₆ are hydrogen: R₃ is C₁₋₂₃ straight orbranched or a cyclic alkyl or alkenyl; alkoxyalkyli halogenated alkyl,phenyl, or benzyl; alkyl phenyl, or benzyl: R₄ is methyl: and R₇ isbenzenesulfonyl; or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl; and X is oxygen or NH.
 4. A method for protecting a cropagainst fungal diseases comprising applying to the crop or its locus acomposition containing an effective amount of a compound having theformula

wherein: a) R₁ and R₂ are independently hydrogen, C₁₋₈ alkyl, phenyl,and phenyl C₁₋₄ alkyl; b) R₃ is C₁₋₂₃ straight or branched or a cyclicalkyl or alkenyl; alkoxyalkyli halogenated alkyl, phenyl, or benzyl;alkyl phenyl; c) R₄ and R₅ are independently hydrogen or C₁₋₈ alkyl; d)R₆ is hydrogen: C₁₋₈ alkyl; C₂₋₃ alkanoyl; phenyl C₁₋₄ alkyl, benzoylwherein the phenyl moiety is optionally substatuted by one or morehalogen atoms or alkyl groups, C₂₋₈ alkoxycarbonyl; CONHR₈ wherein R₈ ishydrogen, C₁₋₃ alkyl, phenyl, phenyl C₁₋₄ alkyl; phenyl C₂₋₄alkyloxycarbonyl; e) R₇ is benzenesulfonyl or benzoyl optionallysubstituted by one or more halogens, alkyl groups, amino groups oralkoxy groups; or thiophene carbonyl; f) X is O, or NH, and saltsthereof.
 5. A method according to claim 4 wherein R₁ and R₂ areindependently hydrogen, R₃ is C₁₋₂₃ straight or branched or a cyclicalkyl or alkenyl; alkoxyalkyli halogenated alkyl, phenyl, or benzyl;alkyl phenyl; optionally substituted by halogen; phenyl or benzyl, R₄and R₅ are independently hydrogen or C₁₋₃ alkyl; R₆ is hydrogen; R₇ isbenzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl; and X is oxygen or —NH.
 6. A method according to claim 4,wherein R₁, R₂, R₅, and R₆ are hydrogen: R₃ is C₁₋₂₃ straight orbranched or a cyclic alkyl or alkenyl; alkoxyalkyli halogenated alkyl,phenyl, or benzyl; R₄ is methyl; and R₇ is benzenesulfonyl or benzoyloptionally substituted by one or more halogens, alkyl groups, aminogroups or alkoxy groups; or thiophene carbonyl; and X is oxygen or NH.7. A method according to claim 4 wherein the compound is applied to thecrop at a dosage rated of from 0.1 to 5 kg/ha.
 8. A method according toclaim 4 wherein the compound is applied to the crop at a dosage rate of0.2 to 2 kg/ha.
 9. A method of protecting tomatoes or potatoes againstEarly Bight or Late Blight comprising of applying to the tomato orpotato plant or its locus an effective amount of the compound having theformula (I)

Wherein: a) R₁ and R₂ are independently hydrogen, C₁₋₈ phenyl, andphenyl C₁₋₄ alkyl b) R₃ is C₁₋₂₃ straight or branched or a cyclic alkylor alkenyl; alkoxyalkyli halogenated alkyl, phenyl, or benzyl; alkylphenyl; c) R₄ and R₅ are independently hydrogen or C₁₋₈ alkyl; d) R₆ ishydrogen; C₁₋₈ alkyl; C₂₋₈ alkanoyl; phenyl C₁₋₄, alkyl, benzoyl whereinthe phenyl moiety is optionally substatuted by one or more halogen atomsor alkyl groups, C₂₋₈ alkoxycarbonyl; CONHR₈ wherein R₈ is hydrogen,C₁₋₈ alkyl, phenyl, phenyl C₁₋₄ alkyl; phenyl C₁₋₄ alkyloxycarbonyl; e)R₇ is benzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl; f) X is O, or NH, and salts thereof.
 10. A method according toclaim 9, wherein R₁ and R₂ are independently hydrogen, R₃ is C₁₋₂₃straight or branched or a cyclic alkyl or alkenyl; alkoxyalkylihalogenated alkyl, phenyl, or benzyl alkyl phenyl; R₄ and R₅ areindependently hydrogen or C₁₋₃ alkyl; R₆ is hydrogen; R₇ isbenzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl; and X is oxygen or —NH.
 11. A method according to claim 9,wherein R₁ and R₂, R₅, and R₆ are hydrogen: R₃ is C₁₋₂₃ straight orbranched or a cyclic alkyl or alkenyl; alkoxyalkyli halogenated alkyl,phenyl, or benzyl; alkyl phenyl; R₄ is methyl; and R₇ is benzenesulfonylor benzoyl optionally substituted by one or more halogens, alkyl groups,amino groups or alkoxy groups; or thiophene carbonyl; and X is oxygen or—NH.
 12. A method according to claim 9 wherein the compound is appliedto the crop at a dosage rated of from 0.1 to 5 kg/ha.
 13. A methodaccording to claim 9 wherein the compound is applied to the crop at adosage rate of 0.2 to 2 kg/ha.
 14. A method for protecting cerealsagainst powdery mildew, by applying to cereal plant or its locus acomposition containing an effective amount of a compound having theformula (I)

wherein, a) R₁ and R₂ are independently hydrogen, C₁₋₈ alkyl, phenyl,and phenyl C₁₋₄ alkyl b) R₃ is C₁₋₂₃ straight or branched or a cyclicalkyl or alkenyl; alkoxyalkyl halogenated alkyl, phenyl, or benzyl;alkyl phenyl; c) R₄ and R₅ are independently hydrogen or C₁₋₈ alkyl; d)R₆ is hydrogen; C₁₋₈ alkyl; C₂₋₈ alkanoyl; phenyl C₁₋₄ alkyl, benzoyolwherein the phenyl moiety is optionally substituted by one or morehalogen atoms or alkyl groups C₂₋₈ alkoxycarbonyl; CONHR₈ wherein R₈ ishydrogen, C₁₋₈ alkyl phenyl, phenyl C₁₋₄ alkyl; phenyl C₂₋₄alkyloxycarbonyl; e) R₇ is benzenesulfonyl or benzoyl optionallysubstituted by one or more halogens, alkyl groups, amino groups oralkoxy groups; or thiophene carbonyl; f) X is O or NH and salts thereof;and the crop is selected from tomatoes, potatoes and cereals.
 15. Amethod according to claim 14, wherein R₁ and R₂ are independentlyhydrogen, R₃ is C₁₋₂₃ straight or branched or a cyclic alkyl or alkenyl;alkoxyalkyli halogenated alkyl, phenyl, or benzyl; alkyl phenyl; R₄ andR₅ are independently hydrogen or C₁₋₃ alkyl; R₆ is hydrogen: R₇ isbenzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl; and X is oxygen or —NH.
 16. A method according to claim 14,wherein R₁, R₂, R₅, and R₆ are hydrogen: R₃ is C₁₋₂₃ straight orbranched or a cyclic all or alkenyl; alkoxyalkyli halogenated alkyl,phenyl, or benzyl; alkyl phenyl, or benzyl: R₄ is methyl: and R₇ isbenzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl; and X is oxygen or NH.
 17. A method according to claim 14wherein the compound is applied post-emergence.
 18. A method accordingto claim 14 wherein the compound is applied to the crop at a dosagerated of from 0.1 to 5 kg/ha.
 19. A method for protecting cucumberagainst downy mildew, by applying to cucumber plant or its locus acomposition containing an effective amount of a compound having theformula (I)

wherein: a) R₁ and R₂ are independently hydrogen, C₁₋₄ alkyl, phenyl,and phenyl C₁₋₄ alkyl b) R₃ is C₁₋₂₃ straight or branched or a cyclicalkyl or alkenyl; alkoxyalkyl halogenated alkyl, phenyl, or benzyl;alkyl phenyl; c) R₄ and R₅ are independently hydrogen or C₁₋₈ alkyl; d)R₆ is hydrogen; C₁₋₈ alkyl; C₂₋₈ alkanoyl; phenyl C₁₋₄ alkyl, benzoyolwherein the phenyl moiety is optionally substituted by one or morehalogen atoms or alkyl groups C₂₋₈ alkoxycarbonyl; CONHR₈ wherein R₈ ishydrogen, C₁₋₈ alkyl, phenyl, phenyl C₁₋₄ alkyl; phenyl C₂₋₄alkyloxycarbonyl; e) R₇ is benzenesulfonyl or benzoyl optionallysubstituted by one or more halogens, alkyl groups, amino groups oralkoxy groups; or thiophene carbonyl; f) X is O or NH and salts thereof;and the crop is selected from tomatoes, potatoes and cereals.
 20. Amethod according to claim 19, wherein R₁ and R₂ are independentlyhydrogen, R₃ is C₁₋₂₃ straight or branched or a cyclic alkyl or alkenyl;alkoxyalkyli halogenated alkyl, phenyl, or benzyl alkyl phenyl; R₄ andR₅ are independently hydrogen or C₁₋₃ alkyl; R₆ is hydrogen; R₇ isbenzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl; and X is oxygen or —NH.
 21. A method according to claim 19,wherein R₁ and R₂, R5, and R₆ are hydrogen: R₃ is C₁₋₂₃ straight orbranched or a cyclic alkyl or alkenyl; alkoxyalkyli halogenated alkyl,phenyl, or benzyl; alkyl phenyl; R₄ is methyl; and R₇ is benzenesulfonylor benzoyl optionally substituted by one or more halogens, alkyl groups,amino groups or alkoxy groups; or thiophene carbonyl and X is oxygen or—NH.
 22. A method according to claim 19 wherein the compound is appliedto the crop at a dosage rated of from 0.1 to 5 kg/ha.
 23. A methodaccording to claim 19 wherein the compound is applied to the crop at adosage rate of 0.2 to 2 kg/ha.
 24. A method for protecting grapesagainst downy mildew, by applying to grape plant or its locus acomposition containing an effective amount of a compound having theformula (I)

wherein: a) R₁ and R₂ are independently hydrogen, C₁₋₈ alkyl, phenyl,and phenyl C₁₋₄ alkyl b) R₃ is C₁₋₂₃ straight or branched or a cyclicalkyl or alkenyl; alkoxyalkyl halogenated alkyl, phenyl, or benzyl;alkyl phenyl; c) R₄ and R₅ are independently hydrogen or C₁₋₈ alkyl; d)R₆ is hydrogen; C₁₋₈ alkyl; C₂₋₈ alkyl; phenyl C₁₋₄ alkyl benzoyolwherein the phenyl moiety is optionally substituted by one or morehalogen atoms or alkyl groups C₂₋₈ alkoxycarbonyl; CONHR₈ wherein R₈ ishydrogen, C₁₋₈ alkyl, phenyl, phenyl C₁₋₄ alkyl; phenyl C₂₋₄alkyloxycarbonyl; e) R₇ is benzenesulfonyl or benzoyl optionallysubstituted by one or more halogens, alkyl groups, amino groups oralkoxy groups; or thiophene carbonyl; f) X is O or NH and salts thereof.25. A method according to claim 24, wherein R₁ and R₂ are independentlyhydrogen, R₃ is C₁₋₂₃ straight or branched or a cyclic alkyl or alkenyl;alkoxyalkyli halogenated alkyl, phenyl, or benzyl alkyl phenyl; R₄ andR₅ are independently hydrogen or C₁₋₃ alkyl; & is hydrogen; R₇ isbenzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl; and X is oxygen or —NH.
 26. A method according to claim 24,wherein R₁ and R₇ R₅, and Pd are hydrogen: R₃ is C₁₋₂₃ straight orbranched or a cyclic alkyl or alkenyl; alkoxyalkyli halogenated alkyl,phenyl, or benzyl; alkyl phenyl; R4 is methyl; and R₇ is benzenesulfonylor benzoyl optionally substituted by one or more halogens, alkyl groups,amino groups or alkoxy groups; or thiophene carbonyl; and X is oxygen or—NH.
 27. A method according to claim 24 wherein the compound is appliedto the crop at a dosage rated of from 0.1 to 5 kg/ha.
 28. A methodaccording to claim 24 wherein the compound is applied to the crop 250 ata dosage rate of 0.2 to 2 kg/ha.
 29. A method for protecting melonsagainst downy mildew, by applying to melon plant or its locus acomposition containing an effective amount of a compound having theformula (I)

wherein: a) R₁ and R₂ are independently hydrogen, C₁₋₈ alkyl, phenyl,and phenyl C₁₋₄ alkyl b) R₃ is C₁₋₂₃ straight or branched or a cyclicalkyl or alkenyl; alkoxyalkyl halogenated alkyl phenyl, or benzyl; alkylphenyl; c) R₄ and R₅ are independently hydrogen or C₁₋₈ alkyl; d) R₆ ishydrogen; C₁₋₈ alkyl; C₂₋₈ alkanoyl; phenyl C₁₋₄ alkyl, benzoyol whereinthe phenyl moiety is optionally substituted by one or more halogen atomsor alkyl groups C₂₋₈ alkoxycarbonyl; CONHR₈ wherein R₈ is hydrogen, C₁₋₈alkyl, phenyl, phenyl C₁₋₄ alkyl; phenyl C₂₋₄ alkyloxycarbonyl; e) R₇ isbenzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl; f) X is O or NH and salts thereof.
 30. A method according toclaim 24, wherein R₁ and R₂ are independently hydrogen; R₃ is C₁₋₂₃straight or branched or a cyclic alkyl or alkenyl; alkoxyalkylihalogenated alkyl phenyl, or benzyl alkyl phenyl; R₄ and R₅ areindependently hydrogen or C₁₋₃ alkyl; R₆ is hydrogen; R₇ isbenzenesulfonyl or benzoyl optionally substituted by one or morehalogens, alkyl groups, amino groups or alkoxy groups; or thiophenecarbonyl; and X is oxygen or —NH.
 31. A method according to claim 24,wherein R₁ and R₂, R5, and R₆ are hydrogen: R₃ is C₁₋₂₃ straight orbranched or a cyclic alkyl or alkenyl; alkoxyalkyli; halogenated alkyl,phenyl, or benzyl; alkyl phenyl; R4 is methyl; and R₇ is benzenesulfonylor benzoyl optionally substituted by one or more halogens, alkyl groups,amino groups or alkoxy groups; or thiophene carbonyl; and X is oxygen or—NH.
 32. A method according to claim 29 wherein the compound is appliedto the crop at a dosage rated of from 0.1 to 5 kg/ha.
 33. A methodaccording to claim 29 wherein the compound is applied to the crop at adosage rate of 0.2 to 2 kg/ha.
 34. A method according to claim 4,wherein the compound is applied to the plant leaves or stems, the plantroots, the soil, or the seeds, tubers or bulbs of the plant.
 35. Amethod according to claim 4, wherein the compound is appliedpre-emergent or post-emergent.
 36. A method according to claim 9,wherein the compound is applied to the plant leaves or stems, the plantroots, the soil, or the seeds, tubers or bulbs of the plant.
 37. Amethod according to claim 9, wherein the compound is appliedpre-emergent or post-emergent.
 38. A method according to claim 14,wherein the compound is applied to the plant leaves or stems, the plantroots, the soil, or the seeds, tubers or bulbs of the plant.
 39. Amethod according to claim 14, wherein the compound is appliedpre-emergent or post-emergent.
 40. A method according to claim 19,wherein the compound is applied to the plant leaves or stems, the plantroots, the soil, or the seeds, tubers or bulbs of the plant.
 41. Amethod according to claim 19, wherein the compound is appliedpre-emergent or post-emergent.
 42. A method according to claim 24,wherein the compound is applied to the plant leaves or stems, the plantroots, the soil, or the seeds, tubers or bulbs of the plant.
 43. Amethod according to claim 24, wherein the compound is appliedpre-emergent or post-emergent.
 44. A method according to claim 29,wherein the compound is applied to the plant leaves or stems, the plantroots, the soil, or the seeds, tubers or bulbs of the plant.
 45. Amethod according to claim 29, wherein the compound is appliedpre-emergent or post-emergent.
 46. A compound according to claim 1,wherein the compound is selected from the group consisting ofD,L-N-benzensulfonyl-3-amino N-benzyl butyramide;D,L-N-benzensulfonyl-3-aminobutyranilide;D,L-N-β-chlorobenzoyl-3-aminobutyric acid-2-chloroethyl ester;D,L-N-β-methyl benzoyl-3-aminobutyric acid, n-octyl ester; N-β-methylbenzoyl-3-aminobutyric acid, sec. butyl ester;D,L-N-3,4,-dichlorobenzoyl-3-aminobutyric acid, n-octyl ester;DL-N-benzoyl-3-aminobutyric acid-2-chloroethyl ester; N-β-methylbenzoyl-3-aminobutyric acid-1-methyl-1-pentyl ester; DL-N-benzenesulfonyl-3-aminobutyric acid, n-octyl ester; N-benzenesulfonyl-3-aminobutyric acid, sec butyl ester; N-benzenesulfonyl-3-aminobutyric acid, 1-methyl-1-butyl ester; D,LN-4-methoxybenzoyl-3-aminobutyric acid heptyl ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid heptyl ester; D,LN-2,6-difluorobenzoyl-3-aminobutyric acid heptyl ester; D,LN-4-tertbutylbenzoyl-3-aminobutyric acid heptyl ester; D,LN-4-methylbenzenesulfonyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzenesulfonyl-3-aminbutyric acid 3-phenylpropyl ester; D,LN-4-cholrobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid 2-(trichloromethyl) ethyl ester;D,L N-4-methylbenzenesulfonyl-3-aminobutyric 1-methylpropyll ester; D,LN-3,4-dimethylbezoyl-3-aminobutyric acid 1-methylbutyl ester; D,LN-3-methylbezoyl-3-aminobutyric acid heptyl ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-2,6-dichlorobenzoyl-3-aminobutyric acid heptyl ester; D,LN-2,6-dichlorobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-4-methylbenzoyl-3-aminobutyric acid 3-phenylpropyl ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid 2-chloroethyl ester; D,LN-4-methoxybenzoyl-3-aminobutyric acid 2-chloroethyl ester; D,LN-benzoyl-3-aminobutyric acid 2-(tricholoromethyl)ethyl ester; D,LN-4-chlorobenzoyl-3-aminobutyric acid heptyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid 1-methyl-2-methoxyethyl ester; D,LN-2-methylbezoyl-3-aminobutyric acid heptyl ester; D,LN-4-methylbenzenesulfonyl-3-aminobutyric acid 2-bromoethyl ester; D,LN-4-methylbenzenesulfonyl-3-aminobutyric acid heptyl ester; D,LN-4-chlorobenzenesulfonyl-3-aminobutyric acid propyl ester; D,LN-4-methylbenzoyl-3-aminobutyric acid 2-(trichloromethyl)ether ester;D,L N-4-methylbenzoyl-3-aminobutyric acid cyclohexyl ester;D,L-N-benzoyl-3-aminobutyric acid cyclohexyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid cyclohexyl ester; D,LN-4-chlorobenzenesulfonyl-3-aminobutyric acid heptyl ester; 44 D,LN-benzenesulfonyl-3-aminobutyric acid propyl ester; D,LN-benzoyl-3-aminobutyric acid 2-propenyl ester; D,LN-4-methylbenzoyl-3-aminobutyric acid 1-methylhexyl ester; D,LN-4-methylbenzoyl-3-amionbutyric acid 1-methyldecanyl ester; D,LN-3,4-dimethylbezoyl-3-aminobutyric acid heptyl ester; D,LN-4-methylbezoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-2-methylaminobenzoyl-3-aminobutyric acid methyl ester; D,LN-4-chlorobenzensulfonyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzensulphonyl-3-aminobutyric acid 3-phenylpropyl ester; D,LN-2-methylaminobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzensulfonyl-3-aminobutyric acid 3,5-dichlorophenyl; D,LN-4-methylaminobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-3,4-dimethylbenzoyl-3-aminobutyric acid octyl ester; D,L,N-2-thiophenecarbonyl-3-aminobutyric acid octyl ester; and D,LN-2-thiophenecarbonyl-3-aminobutyric acid 1-methylpentyl ester.
 47. Acompound according to claim 4, wherein the compound is selected from thegroup consisting of D,L-N-benzensulfonyl-3-amino N-benzyl butyramide;D,L-N-benzensulfonyl-3-aminobutyranilide;D,L-N-β-chlorobenzoyl-3-aminobutyric acid-2-chloroethyl ester;D,L-N-β-methyl benzoyl-3-aminobutyric acid, n-octyl ester; N-β-methylbenzoyl-3-aminobutyric acid, sec. butyl ester;D,L-N-3,4,-dichlorobenzoyl-3-aminobutyric acid, n-octyl ester;DL-N-benzoyl-3-aminobutyric acid-2-chloroethyl ester; N-β-methylbenzoyl-3-aminobutyric acid-1-methyl-1-pentyl ester; DL-N-benzenesulfonyl-3-aminobutyric acid, n-octyl ester; N-benzenesulfonyl-3-aminobutyric acid, sec butyl ester; N-benzenesulfonyl-3-aminobutyric acid, 1-methyl-1-butyl ester; D,LN-4-methoxybenzoyl-3-aminobutyric acid heptyl ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid heptyl ester; D,LN-2,5-difluorobenzoyl-3-aminobutyric acid heptyl ester; D,LN-4-tertbutylbenzoyl-3-aminobutyric acid heptyl ester; D,LN-4-methylbenzenesulfonyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzenesulfonyl-3-aminbutyric acid 3-phenylpropyl ester; D,LN-4-cholrobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid 2-(trichoromethyl) ethyl ester;D,L N-4-methylbenzenesulfonyl-3-aminobutyric 1-methylpropyll ester; D,LN-3,4-dimethylbezoyl-3-aminobutyric acid 1-methylbutyl ester; D,LN-3-methylbezoyl-3-aminobutyric acid heptyl ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-2,6-dichlorobenzoyl-3-aminobutyric acid heptyl ester; D,LN-2,6-dichlorobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-4-methylbenzoyl-3-aminobutyric acid 3-phenylpropyl ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid 2-chloroethyl ester; D,LN-4-methoxybenzoyl-3-aminobutryic acid 2-chloroethyl ester; D,LN-benzoyl-3-aminobutyric acid 2-(tricholoromethyl)ethyl ester; D,LN-4-chlorobenzoyl-3-aminobutyric acid heptyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid 1-methyl-2-methoxyethyl ester; D,LN-2-methylbezoyl-3-aminobutyric acid heptyl ester; D,LN-4-methylbenzenesulfonyl-3-aminobutyric acid 2-bromoethyl ester; D,LN-4-methylbenzenesulfonyl-3-aminobutyric acid heptyl ester; D,LN-4-chlorobenzenesulfonyl-3-aminobutyric acid propyl ester; D,LN-4-methylbenzoyl-3-aminobutyric acid 2-(trichloromethyl)ether ester;D,L N-4-methylbenzoyl-3-aminobutyric acid cyclohexyl ester;D,L-N-benzoyl-3-aminobutyric acid cyclohexyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid cyclohexyl ester; D,LN-4-chlorobenzenesulfonyl-3-aminobutyric acid heptyl ester; 44 D,L N—benzenesulfonyl-3-aminobutyric acid propyl ester; D,LN-benzoyl-3-aminobutyric acid 2-propenyl ester; D,LN-4-methylbenzoyl-3-aminobutyric acid 1-methylhexyl ester; D,LN-4-methylbenzoyl-3-amionbutyric acid 1-methyldecanyl ester; D,LN-3,4-dimethylbezoyl-3-aminobutyric acid heptyl ester; D,LN-4-methylbezoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-2-methylaminobenzoyl-3-aminobutyric acid methyl ester; D,LN-4-chlorobenzensulfonyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzensulphonyl-3-aminobutyric acid 3-phenylpropyl ester; D,LN-2-methylaminobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzensulfonyl-3-aminobutyric acid 3,5-dichlorophenyl; D,LN-4-methylaminobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-3,4-dimethylbenzoyl-3-aminobutyric acid octyl ester; D,L,N-2-thiophenecarbonyl-3-aminobutyric acid octyl ester; and D,LN-2-thiophenecarbonyl-3-aminobutyric acid 1-methylpentyl ester.
 48. Acompound according to claim 9, wherein the compound is selected from thegroup consisting of D,L-N-benzensulfonyl-3-amino N-benzyl butyramide;D,L-N-benzensulfonyl-3-aminobutyranilide;D,L-N-β-chlorobenzoyl-3-aminobutyric acid-2-chloroethyl ester;D,L-N-β-methyl benzoyl-3-aminobutyric acid, n-octyl ester; N-β-methylbenzoyl-3-aminobutyric acid, sec. butyl ester;D,L-N-3,4,-dichlorobenzoyl-3-aminobutyric acid, n-octyl ester;DL-N-benzoyl-3-aminobutyric acid-2-chloroethyl ester; N-β-methylbenzoyl-3-aminobutyric acid-1-methyl-1-pentyl ester; DL-N-benzenesulfonyl-3-aminobutyric acid, n-octyl ester; N-benzenesulfonyl-3-aminobutyric acid, sec butyl ester; N-benzenesulfonyl-3-aminobutyric acid, 1-methyl-1-butyl ester; D,LN-4-methoxybenzoyl-3-aminobutyric acid heptyl ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid heptyl ester; D,LN-2,6-difluorobenzoyl-3-aminobutyric acid heptyl ester; D,LN-4-tertbutylbenzoyl-3-aminobutyric acid heptyl ester; D,LN-4-methylbenzenesulfonyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzenesulfonyl-3-aminbutyric acid 3-phenylpropyl ester; D,LN-4-cholrobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid 2-(trichloromethyl) ethyl ester;D,L N-4-methylbenzenesulfonyl-3-aminobutyric 1-methylpropyll ester; D,LN-3,4-dimethylbezoyl-3-aminobutyric acid 1-methylbutyl ester; D,LN-3-methylbezoyl-3-aminobutyric acid heptyl ester; D,LN-4-chlorobenzenesulfonyl-3-aminobutyric acid propyl ester; D,LN-4-methylbenzoyl-3-aminobutyric acid 2-(trichloromethyl)ether ester;D,L N-4-methylbenzoyl-3-aminobutyric acid cyclohexyl ester;D,L-N-benzoyl-3-aminobutyric acid cyclohexyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid cyclohexyl ester; D,L,N-2-thiophenecarbonyl-3-aminobutyric acid octyl ester; D,LN-2-thiophenecarbonyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-2-methylaminobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid 3-phenylpropyl ester; and D,LN-4-chlorobenzenesulfoyl-3-aminobutyric acid 1-methylpentyl ester.
 49. Acompound according to claim 14, wherein the compound is selected fromthe group consisting of D,L-N-benzensulfonyl-3-amino N-benzylbutyramide; D,L-N-benzensulfonyl-3-aminobutyranilide;D,L-N-β-chlorobenzoyl-3-aminobutyric acid-2-chloroethyl ester;D,L-N-β-methyl benzoyl-3-aminobutyric acid, n-octyl ester; N-β-methylbenzoyl-3-aminobutyric acid, sec. butyl ester;D,L-N-3,4,-dichlorobenzoyl-3-aminobutyric acid, n-octyl ester;DL-N-benzoyl-3-aminobutyric acid-2-chloroethyl ester; N-β-methylbenzoyl-3-aminobutyric acid-1-methyl-1-pentyl ester; DL-N-benzenesulfonyl-3-aminobutyric acid, n-octyl ester; N-benzenesulfonyl-3-aminobutyric acid, sec butyl ester; N-benzenesulfonyl-3-aminobutyric acid, 1-methyl-1-butyl ester; D,LN-4-methoxybenzoyl-3-aminobutyric acid heptyl ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid heptyl ester; D,LN-4-tertbutylbenzoyl-3-aminobutyric acid heptyl ester; D,LN-4-methylbenzenesulfonyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-2-methylbezoyl-3-aminobutyric acid heptyl ester; D,LN-4-chlorobenzenesulfonyl-3-aminobutyric acid propyl ester;D,L-N-benzoyl-3-aminobutyric acid cyclohexyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid cyclohexyl ester; D,LN-benzoyl-3-aminobutyric acid 2-propenyl ester; D,LN-4-methylbenzoyl-3-aminobutyric acid 1-methylhexyl ester; D,LN-4-methylbenzoyl-3-amionbutyric acid 1-methyldecanyl ester; D,LN-3,4-dimethylbezoyl-3-aminobutyric acid heptyl ester; D,LN-2-methylaminobenzoyl-3-aminobutyric acid methyl ester; D,LN-2-methylaminobenzoyl-3-aminonutyric acid methyl ester; D,LN-4-methylbezoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-4-chlorobenzensulfonyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-2-methylaminobenzoyl-3-aminobutyric acid methyl ester; D,LN-3,4-dimethylbenzoyl-3-aminobutyric acid octyl ester; and D,LN-benzensulfonyl-3-aminobutyric acid 3,5-dichlorophenyl.
 50. A compoundaccording to claim 19, wherein the compound is selected from the groupconsisting of D,L N-4-chlorobenzenesulfonyl-3-aminobutyric acid propylester; D,L N-4-methylbenzoyl-3-aminobutyric acid2-(trichloromethyl)ether ester; D,L N-4-methylbenzoyl-3-aminobutyricacid cyclohexyl ester; D,L-N-benzoyl-3-aminobutyric acid cyclohexylester; D,L N-benzenesulfonyl-3-aminobutyric acid cyclohexyl ester; D,LN-4-chlorobenzenesulfonyl-3-aminobutyric acid heptyl ester; and D,LN-2-methylaminobenzoyl-3-aminobutyric acid 1-methylpentyl ester.
 51. Acompound according to claim 24, wherein the compound is selected fromthe group consisting of D,L N-2,6-difluorobenzoyl-3-aminobutyric acidheptyl ester; D,L N-4-tertbutylbenzoyl-3-aminobutyric acid heptyl ester;D,L N-4-methylbenzenesulfonyl-3-aminobutyric acid 1-methylpentyl ester;D,L N-benzenesulfonyl-3-aminbutyric acid 3-phenylpropyl ester; D,LN-4-cholrobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid 2-(trichloromethyl)ethyl ester;D,L N-4-methylbenzenesulfonyl-3-aminobutyric 1-methylpropyll ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-2,6-dichlorobenzoyl-3-aminobutyric acid heptyl ester; D,LN-2,6-dichlorobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-4-methylbenzoyl-3-aminobutyric acid 3-phenylpropyl ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid 2-chloroethyl ester; D,LN-4-methoxybenzoyl-3-aminobutryic acid 2-chloroethyl ester; D,L N—benzoyl-3-aminobutyric acid 2-(tricholoromethyl)ethyl ester; D,LN-4-chlorobenzoyl-3-aminobutyric acid heptyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid 1-methyl-2-methoxyethyl ester; andD,L N-benzenesulfonyl-3-aminobutyric acid 3-phenylpropyl ester.
 52. Acompound according to claim 24, wherein the compound is selected fromthe group consisting of D,L N-4-methoxybenzoyl-3-aminobutyric acidheptyl ester; D,L N-4-tertbutylbenzoyl-3-aminobutyric acid heptyl ester;D,L N-benzenesulfonyl-3-aminbutyric acid 3-phenylpropyl ester; D,LN-4-cholrobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-benzenesulfonyl-3-aminobutyric acid 2-(trichloromethyl)ethyl ester;D,L N-3-methylbezoyl-3-aminobutyric acid heptyl ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-2,6-dichlorobenzoyl-3-aminobutyric acid 1-methylpentyl ester; D,LN-3,5-dimethylbezoyl-3-aminobutyric acid 2-chloroethyl ester; D,LN-benzoyl-3-aminobutyric acid 2-(tricholoromethyl)ethyl ester; D,LN-2-methylbezoyl-3-aminobutyric acid heptyl ester; D,LN-4-methylbenzenesulfonyl-3-aminobutyric acid 2-bromoethyl ester; D,LN-4-methylbenzenesulfonyl-3-aminobutyric acid heptyl ester; and D,LN-benzenesulfonyl-3-aminobutyric acid 3-phenylpropyl ester.